The county was formed in 1779 from the northern half of Bute County. It was named for Joseph Warren of Massachusetts, a physician and general in the American Revolutionary War who was killed at the Battle of Bunker Hill. Developed as tobacco and cotton plantations, the county generated considerable wealth in the antebellum years, built on the labor of slaves. Its county seat of Warrenton became a center of commerce and was one of the wealthiest towns in the state from 1840 to 1860. Many planters built fine homes there.
In 1881, parts of Warren County, Franklin County, and Granville County were combined to form Vance County. In the late nineteenth and twentieth centuries, the county's continued reliance on agriculture slowed its development. Many residents migrated to cities for work.
Warren County is the site of Soul City, a "planned community" development of the late twentieth century funded by the Department of Housing and Urban Development (HUD). It has not been successful in attracting business and industry, and has not developed as much housing as intended.
Beginning in 1982, Warren County was the site of the Warren County PCB Landfill. Residents of the county have pursued a long environmental justice struggle to remove dangerous pollutants from the site, to improve the health of citizens. The site was not made safe until 2004.